Thiophosphate derivatives of triazoline thiones

ABSTRACT

A NOVEL COMPOSITION OF MATTER COMPRISING PHOSPHATE DERIVATIVES OF $2-1,2,4-TRIAZOLINE COMPOUNDS HAVING TIGHTLY DESIRABLE UTILITY AS INSECTICIDES AND ACARICIDES.

United States Patent 3,719,686 THIOPHOSPHATE DERIVATIVES OF TRIAZOLINETHIONES Tony Cebalo, Allentown, Pa., assignor to Air Products andChemicals, Inc., Allentown, Pa.

No Drawing. Continuation-impart of application Ser. No. 835,221, June20, 1969. This application Apr. 28, 1970, Ser. No. 32,715

Int. Cl. C07f 9/16, 9/24, 9/40 US. Cl. 260-308 C 11 Claims ABSTRACT OFTHE DISCLOSURE A novel composition of matter comprising phosphatederivatives of A -1,2,4-triaz0line compounds having highly desirableutility as insecticides and acaricides.

BACKGROUND OF THE INVENTION This application is a continuation-in-partapplication of Ser. No. 835,221, filed June 20, 1969, now abandoned.

The present invention relates to the synthesis of novel compositionscomprising phosphate derivatives of certain 3-substituted-A-1,2,4-triazoline compounds. More particularly, it relates to phosphatederivatives of 3-flu0roalkyl-A 1,2,4-triazoline--thiones and3-chlorodifiuoromethyl A 1,2,4 triazoline-S-thiones compounds which havedesirable use as insecticides and acaricides. Furthermore, it relates tomethods for using such compounds in various agricultural applications.

A somewhat related compound is shown in the art, for example,1-diethoxyphosphinothioylthiomethyl-3,4- dimethyl-A-1,2,4-triazoline-5-thione [1. Sci. Fd. Agric., 19, 475-80 (1968). Suchcompound is reported to have both insecticidal and acaricidal activity.The compound is only generally related to those compounds of the presentinvention.

SUMMARY OF THE INVENTION The present invention relates to phosphatederivatives of A -1,2,4-triazoline-5-thione compounds and may be broadlyrepresented as having the structure:

i R3 NE-TNCHZXP R4 R1 4 5 -S 5 R: (I)

wherein R represents fluoroalkyl radicals having from 1 to 7 carbonatoms or a chlorodifiuoromethyl radical,

R represents lower alkyl radicals having from 1 to 7 carbon atoms,

R and R independently represent alkyl, alkoxy or alkylamino radicalshaving from 1 to 7 carbon atoms or phenyl radicals, and

X and Y are independently oxygen or sulfur.

3,719,686 Patented Mar. 6, 1973 wherein R represents fiuoroalkylradicals having from 1 to 7 carbon atoms or a chlorodifiuoromethylradical, and

R represents lower alkyl radicals having from 1 to 7 carbon atoms.

Also included in the scope of the present invention are otherintermediate triazoline compounds having the general structure:

(III) wherein R represents fluoroalkyl radicals having from 1 to 7carbon atoms or a chlorodifiuoromethyl radical, and

R represents lower alkyl radicals having from 1 to 7 carbon atoms.

Furthermore, included within the scope of the present invention arestill other intermediate triazoline compounds having the generalstructure:

wherein R represents fiuoroalkyl radicals having from 1 to 7 carbonatoms or a chlorodifiuoromethyl radical R represents lower alkylradicals having from 1 to 7 carbon atoms, and

Z represents a halogen such as chlorine, bromine or iodine.

The symbols R R R and R have the same representations throughout thespecification and claims.

Although the compounds represented by the Structures (II), (III), and(IV) have not demonstrated any particular insecticidal or acaricidalproperties, they have utility in the preparation of the compoundsrepresented by Structure (I) which has shown a high degree of activityas a broad spectrum insecticide and acaricide.

PREFERRED EMBODIMENTS OF THE INVENTION The preferred route forsynthesizing the compounds of the present invention involves severalsteps. The first step involves synthesizing A-1,2,4-triazoline-5-thiones having the structure previously given as(II). Such compounds may be synthesized in accordance with one or moreof the following equations:

( refluxing benzene or xylene R COOH HZNNHCNHRZ (H) l azeotrope benzene(R CO) O HZNNHONHRZ RiCONHNHCNHRi l or CFaCOOH S method will becomeobvious to those skilled in the art from the teachings herein set forth.

The particular carboxylic acids used in the above methods arecommercially available or can be made by known methods. Thethiosemicarbazides are, similarly, either available or can besynthesized by standard methods such as for example, the reaction ofhydrazine hydrate with an appropriate isothiocyanate (R NCS).

The compounds having the Structure (-II) may be reacted with aldehydessuch as formaldehyde, acetaldehyde, propionaldehyde and the like toobtain the compounds of Structure (III), e.g.1-hydroxymethyl-4-methyl-3-trifluoromethyl-M-1,2,4-triazoline--thione.

The hydroxymethyl derivatives may be reacted with compounds such asthionyl chloride, phosphorous pentachloride, phosphorous tribromide andthe like to obtain the compounds of Structure (IV), e.g. l-chloromethyl-4-methyl 3 trifiuoromethyl-A -l,2,4-triazoline-S-thione. The abovesynthesis is generally carried out in an inert organic solvent such asbenzene, chloroform and the like at temperatures of less than 70 C. inan inert atmosphere such as nitrogen.

The final products of Structure I may be produced from, for example,1-hydroxymethyl-4-methyl-3-haloalkyl-A -1,2,4-triazoline-5-thiones(Structure III) or corresponding l-halomethyl compounds (Structure IV)by employing various methods known in the art. Examples of some suchmethods are as follows:

in it.

wherein R and R are independently alkyl, alkylamino, alkoxy or phenyl 2.

S CsH S S HSI 3. NNOH2OH II ll NNCH2OP (R3) 4) wherein R and R areindependently alkyl, alkylamino, alkoxy or phenyl wherein R is alkyl,alkylamino, alkoxy or phenyl R is alkyl 1 RiNHi s NNCH201 (Ra)(HNR4)R1-\N/=S l.

wherein R is alkyl, alkylamino, alkoxy or phenyl R is alkyl N--NCHZOHN-N OHZO i (R3) (R4) R NJ=S o1f(R3)(Ri) RIL =s it. 1'1.

wherein R and R are alkoxy.

The above reactions can be carried out in water or organic solvents suchas, for example, benzene, methanol, ethanol, acetone, butanone, ethylacetate and the like at from about room temperature to about C.

It has been found that the compounds of the invention having theStructure (I) are particularly distinguished by the presence of afluoroalkyl or chlorodifluoromethyl group in the 3 position of theparticular phosphate derivatives of A -1,2,4-triazoline compounds. Suchcompounds have exhibited excellent insecticidal and acaricidalproperties. Certain of the compounds show excellent ovicidal properties,whereas somewhat related compounds currently known in the art are absentsuch activity. Certain members of the Structure (I) compounds of thepresent invention have relatively high LD values and yet exhibitexcellent insecticidal and acaricidal properties.

The compounds of the invention having the Structure (I) may beformulated in a variety of ways and concentrations for the purpose ofemploying them for insecticidal and/or acaricidal purposes. It isrecognized that the particular type and concentration of formulation, aswell as the mode of application of the active ingredient may control itsbiological activity in a given application.

Compounds of the invention may be prepared as simple solutions of theactive ingredient in an appropriate solvent in which it is completelysoluble at the desired concentration. Such solvent systems includewater, alcohols, acetone, and other organic solvents. These simplesolutions may be further modified by the addition of varioussurfactants, emulsifying or dispersing agents, colorants, odorants,anti-foaming agents, other pesticides or dormant oils which supplementor synergize the activity of the pesticides of the invention, or otheradjuvants for any given application where deemed desirable to impart aparticular type of biological response.

Compounds of the invention may also be formulated in various other typesof formulations commonly recognized by those skilled in the art ofagricultural or industrial chemicals. These formulations include, forexample, compositions containing the active ingredient as granules ofrelatively large particle size, powder dusts, as wettable powders, asemulsifiable concentrates, as aerosol spray formulations, or as aconstituent part of any other known type of formulation commonlyutilized by those skilled in the art. Such formulations include theadjuvants and carriers normally employed for facilitating the dispersionof active ingredient for agricultural and industrial applications ofpesticidal chemicals. These formulations may contain as little as 0.25%or more than 95% by weight of the active ingredient.

Dust formulations are prepared by mixing the active ingredient withfinely divided solids which act as dispersants and carriers for theingredient in applying it to the locus of application for the desiredcontrol. Typical solids which may be utilized in preparing dustformulations of the active ingredients of the invention include talc,kieselguhr, finely divided clay, fullers earth, or other common organicor inorganic solids. Solids utilized in preparing dust formulations ofthe active ingredient normally have a particle size of 50 microns orless. The active ingredient of these dust formulations is presentcommonly from as little as 0.25 to as much as 30% or more by weight ofthe composition. Granular formulations of the active ingredients areprepared by impregnating or adsorbing the toxicant on or into relativelycoarse particles of inert solids such as sand, attapulgite clay, gypsum,corn cobs or other inorganic or organic solids. The active ingredient ofthese granular formulations is commonly present from 1.0% to as much as20% or more by weight of the composition.

Wettable powder formulations are solid compositions of matter whereinthe active ingredient is absorbed or adsorbed in or on a sorptivecarrier such as finely divided clay, talc, gypsum, lime, wood flour,fullers earth, kieselguhr, or the like. These formulations preferablywere made to contain 50% to 80% of active ingredient. These wettablepowder formulations commonly contain a small amount of Wetting,dispersing or emulsifying agent to facilitate dispersion in water orother liquid carrier utilized to distribute the ingredient to the locusfor the desired control.

Emulsifiable concentrate formulations are homogeneous liquid or pastecompositions containing the active ingredient which will disperse inwater or other liquid carrier to facilitate application of theingredient to the locus for desired control. Such emulsifiableconcentrate formulation of the active ingredients may contain only theactive ingredient with a liquid or solid emulsifying agent or maycontain other relatively nonvolatile organic solvents such asisophorone, dioxane, heavy aromatic naphthas, xylene, or dimethylformamide. The active ingredient in such formulations commonly comprises10.0% to 70.0% by weight of the active ingredient.

Aerosol spray formulations of the toxicants may be prepared wherein theactive ingredient is dispersed in a finely divided form as a result ofvaporization of a low boiling dispersant solvent carrier such as Freons.

The compounds of the present invention having the Structure (I) arecompatible with other pesticides, bactericides, fungicides and the liketo obtain desired biological activity.

The following examples are illustrative of the present invention and arenot intended to limit the scope thereof.

EXAMPLES (I) Synthesis of intermediate compounds EXAMPLE 1 (a) Asolution containing four grams of4-methyl-ltrifiuoroacetylthiosemicarbazide and 30 mls. of a aqueoussodium carbonate solution was refluxed for about 2 hours. The mixturewas cooled to about 10 C. and acidified with hydrochloric acid to yielda solid crude product. The crude product was recrystallized from amethylene chloride-petroleum ether medium to provide a final producthaving a'melting point of 1l9l20 C. The final product was identified as4-methyl-3-trifluoromethyl- A l,2,4 triazoline-S-thione.

C H N SF Required (percent): C, 26.25; H, 2.20; N, 22.96. Found(percent): C, 25.90; H, 2.16; N, 22.92.

(b) Ten and one-half grams of 4-methyl-thiosemicarbazide were placedinto a solution containing 100 mls. of xylene and 10.6 gms. ofdifluoroacetic acid and the EXAMPLE 2 (a) Twenty grams of the compoundas produced in accordance with the procedure of Example 1(a) and 21 gms.of a 37% aqueous solution of formaldehyde were heated together at atemperature of 60 C. about 1 hour at which time a complete solution wasobtained. The reaction mixture was concentrated under vacuum and theresidue dissolved in mls. of ethyl acetate. The ethyl acetate solutionwas dried over anhydrous sodium sulfate and concentrated under vacuum toyield an oil which solidified to wax on standing. The product recovered(21 gms.) was identified as l-hydroxymethyl-4-methyl-3-trifluoromethyl-M-1,2,4-triazoline-S-thione.

Further compounds of the Structure (III), listed in the following tableare prepared in accordance with the above procedures No. R1 2 CFa z s 2CHFQ CH3 3.- CHF; C Hn CgF5 CH3 5 CH1 CH3 CHCHz- 6 CClF CH EXAMPLE 3 (a)Twenty-one grams of the product produced In Example 2 was admixed in around bottom flask with a mixture of 53 mls. of benzene and 25.6 mls. ofthionyl chloride, said mixture having been previously cooled to about 5C. by means of an ice bath. The total mixture was obtained in a nitrogenatmosphere. Nitrogen was bubbled through the resulting mixture untilthere was no evolution of hydrogen chloride gas. The reaction mixturewas subsequently concentrated under vacuum. The resulting product (21gms.) was crystallized from petroleum ether and the melting point wasdetermined to be 40-43" C. The product recovered was identified to bel-chloromethyl-4-methyl 3 trifluoromethyl-A -1,2,4-triazoline- 5-thione.

C H CIF N S.-Required (percent): C, 25.88; H, 2.17; N, 18.11. Found(percent): C, 26.01; H, 2.33; N, 18.16.

Further compounds of the Structure (IV), listed in the following tableare prepared in accordance with the above procedures (1) Four grams ofthe product produced in Example 3(a) and 3.5 gms. of ammoniumdiethyldithiophosphatc Were refluxed in 200 mls. of acetone for about 3hours. The reaction mixture was cooled to about 10 C. filtered and thefiltrate concentrated under vacuum to an oil which solidified on coolingto room temperature. The resulting product was crystallized from aqueousmethanol to produce 5 gms. of a product having a melting point of 88-90"C. The product recovered was identified to be1-diethoxyphosphinothioylthiomethyl 4 methyl-3-trifiuoromethyl-A-1,2,4-triazoline-5 [4H] -thione.

C I-I N F O S P.Required (percent): C, 28.37; H, 3.97; N, 11.03. Found(percent): C, 28.58; H, 3.90; N, 11.00.

Further compounds of the Structure (1), listed in the following tableare prepared in accordance with the above procedures.

No. R R2 a 4 C 11 021-15 0 (3211 CH3 OCHs OCH3 CH3 i-O CaHr i-O 03H? CH30 CH3 0 CH3 CH3 00 11 OC H5 CH3 OCz 5 0 2 5 ClrHa 0 02115 O C 11 CH3 0011 OCgHs CH3 OC H5 007115 EXAMPLE 5 A mixture of 10.0 gms. of theproduct produced in Example 3(a), 11.0 gms. of diphenylphosphinodithioicacid [(C H PSSH] and 4.4 gms. of triethylamine in benzene was refluxedfor three hours. The solids were filtered from the cooled reactionmixture and the benzene filtrate concentrated, under vacuum to an oil.The oil was crystallized from benzene-light petroleum mixture to give aproduct identified to be l-diphenylphosphinothioylthiomethyl-4-methyl 3trifluoromethy1-A -1,2,4- triazoline-5[4H]-thione, which had a meltingpoint of 123126 C.

EXAMPLE 6 A mixture of 8.0 gms. of the product produced in Example 2(a),6.6 gms. of ethyl phosphorochloridate [(C H O) POCl] and 5.2 mls. oftriethylamine in benzene was refluxed for three hours and then allowedto stir at room temperature overnight. The solids were filtered oil andthe filtrate concentrated to an oil. The oil was washed with a 2%aqueous sodium carbonate solution and the residue extracted with diethylether. The ether extract was dried over anhydrous sodium sulphate andconcentrated to a residual oil which was identified to bel-diethoxyphosphinomethyl-4-methyl 3 triflu0r0methyl-A -1,2,4-triazoline-S [4H1-thione.

EXAMPLE 7 A mixture of 8.0 gms. of the product produced in Example 2(a),4.2 gms. of ethyl phosphorochloridothioate [(C H O) PSCl] and 5.4 mls.of triethylamine was refluxed in benzene for three hours and thenallowed to stir at room temperature overnight. The insolubles werefiltered otf and the filtrate concentrated to an oil. The oil was washedwith a 2% aqueous sodium carbonate mixture and the insolubles extractedwith diethyl ether. The ether was dried over anhydrous sodium sulphateand concentrated to a residual oil which was identified to be 1-diethoxyphosphinothioylmethyl-4-methyl 3 trifluoromethyl-A1,2,4-triazoline-5 [4H] -thione.

EXAMPLE 8 A mixture of 6.0 gms. of the product produced in Example 2(a),4.6 gms. of ethylphosphorodichloridothioite [C H PSCI and 4 mls. oftriethylamine in mls. of benzene was stirred at room temperatureovernight. The insolubles were filtered oil and the filtrateconcentrated to a residual oil which was washed with a 2% aqueous sodiumcarbonate solution. The residue was extracted with ether, the etherextract dried over anhydrous sodium sulphate and concentrated to aresidual oil.

A mixture containing the reaction produced above (5.2 gms.), absoluteethanol (0.7 gms.) and triethylamine (1.5 gms.) was refluxed in 50 mls.of benzene for three hours. The cooled reaction mixture was filtered andthe filtrate concentrated to a residual oil which was washed with a 2%aqueous sodium carbonate solution. The residue was extracted withdiethyl ether, the diethyl ether dried over anhydrous sodium sulphateand was then concentrated to an oil which was identified to bel-ethoxy-lethylphosphinylthioylmethyl 4 methyl-3-trifluoromethyl-A-1,2,4-triazoline-5 [4H] -thione.

(III) Insecticidal and acaricidal activity Various compounds of Example4 and those'of other examples having the Structure (I) were tested forbiological activity for controlling a variety of insects and acarids.The following discussion sets forth the method employed to conduct testson specific pests and the corresponding tables include the resultsobtained therefrom. Such tests and results are illustrative only and arenot intended to limit the scope of the biological activity of variouscompounds having the Structure (1).

(A) Tests conducted with the Mexican Bean Beetle The compounds weredissolved in acetone and diluted to appropriate concentrations inde-ionized water containing suitable wetting and emulsifying agents.Foliar portions of cranberry bean plants in first true leaf growth stagewere dipped into an agitated test solution containing a specificcompound, allowed to air dry and placed on holding racks provided with asubterranean water source. Three test plants were used for each chemicaldilution.

After the plants were dried, ten (10) third-instar larvae of the MexicanBean Beetle (Epilachna varz'vestz's) were caged on the tested plants fora period of forty-eight (48) hours. Observations for insect mortalitywere made at the end of the forty-eight (48) hour period. The resultsare set forth in Table I below.

9 (B) Tests conducetd with the Southern Army Worm The proceduredescribed in A above was substantially repeated to determine thetoxicity of the compounds against the Southern Army Worm. The results ofsuch (E) Tests for residual toxicity Representative compounds, havingthe Structure (I) and prepared as described in Example 4, were testedfor residual toxicity of chemical deposit of foliage of treated plants.Chemical solutions of the compounds were prepared and applied inaccordance with the procedures described in A above. The larvae of theMexican Bean Beetle were employed in the particular tests. Insectmortality was determined seventy-two (72) hours after the larvae wereintroduced and caged on the treated foliage. The table shows the degreeof activity against the larvae at various time intervals after initialtreatment of the foliage. The results are set forth in Table V below.

TABLE V Percent mortality (72 hours) Age of residue P.p.m. day 4 days 7days 15 days 22 days 27 days Compound of Example Number:

(C) Tests conducted with the Pea Aphid TABLE III Percent mortalityConcentration, p.p.m 500 250 Compound of Example Number:

(D) Test conducted with acarid s Chemical test solutions were preparedas described in A above. Cranberry bean plants infested with mixed lifestages of two-spotted spider mites (Tetranychus ielarius) were dippedinto the chemical solutions. The plants were air dried and subsequentlyplaced on holding racks provided with a subterranean water source. Threetest plants were used for each chemical treatment. Forty-eight (48)hours after chemical treatment mite mortality was observed. The resultsare set forth in Table IV below.

TABLE IV Percent mortality Concentration, p.p.m 500 250 125 50 25 10 5Compoggrd of Example (F) Systemic insecticidal activity Cranberry beanplants in the first true leaf growth stage and in soil of low moisturecontent were treated with 20 mls. of an aqueous solution of a compoundhaving the Structure (1), said solution being applied as a surfacedrench. All treatments were applied in triplicate. Twenty-four (24)hours after such application, the plants were subjected to continuoussubterranean watering for seventy-two (72) hours. Forty-eight (48) hoursafter application of the solution to the soil, adult Pea Aphids weretransferred to and caged on the foliar portions of the plants for aperiod of forty-eight (48) hours. Insect mortality was observedseventy-two (72) hours after the insects were exposed to feeding on thefoliage. The results are set forth in Table VI below.

(G) Ovicidal activity Certain of the compositions have also shown highlydesirable results as an ovicide. Liquid compositions prepared asdescribed above were contacted with a foliar surface having the eggs ofvarious insects and mites attached thereto at concentrations set forthin the table below. Ovicidal indicates the percent of total eggs thatdid not hatch. Residual indicates the percent of emerged young that diedupon contact with the treated foliar surface. The results were takenafter a six (6) day exposure of the eggs and emerged young to thecompositions. The compositions identification N0. is taken from Example4.

Percent control From the results shown in the tables above, it canreadily be seen that compositions of the present invention having theStructure (I) generally show excellent insecticidal and acaricidalproperties.

1 1 What is claimed is: 1. A composition having the general structure:

wherein R represents fiuoroalkyl radicals having from 1 to 7 carbonatoms or a chlorodifiuoromethyl radical, R represents lower alkylradicals having from 1 to 7 carbon atoms, and R and R independentlyrepresent alkoxy radicals having from 1 to 7 carbon atoms. 2. Thecomposition according to claim 1 wherein R is trifluoromethyl, R ismethyl, and R and R are ethoxy. 3. The composition according to claim 1wherein R is trifiuoromethyl, R is ethyl, and R and R are ethoXy. 4. Thecomposition according to claim 1 wherein R is trifl-uoromethyl, R ismethyl, and R and R are methoxy. 5. The composition according to claim 1wherein R is trifluoromethyl, R is methyl, and R and R are isopropoxy.

6. The composition according to claim 1 wherein R is pentafluoroethyl, Ris methyl, and R and R are methoxy.

7. The composition according to claim 1 wherein R is pentafiuoroethyl, Ris methyl, and R and R are ethoxy.

8. The composition according to claim 1 wherein R is difluoromethyl, Ris methyl, and R and R are ethoxy.

9. The composition according to claim 1 wherein R is difiuoromethyl, Ris butyl, and R and R are ethoxy.

10. The composition according to claim 1 wherein R is2-trifiuoromethylpropyl, R is methyl, and R and R are ethoxy.

11. The composition according to claim 1 wherein R ischlorodifluoromethy-l, R is methyl, and R and R are ethoxy.

References Cited UNITED STATES PATENTS 3,594,390 7/1971 Timmler et a1.260-308 FOREIGN PATENTS 713,278 8/1954 Great Britain 260308 OTHERREFERENCES Pianka, J. Sci. Fd. Agric., vol. 19, pp. 475-480 (1968) (Sci.Lib.).

ALTON D. ROLLINS, Primary Examiner US. Cl. X.'R.

